Blocking microglial reactivity via purinergic receptors prevents subacute cognitive deficits after TIA

Llovera, Gemma; Heindl, Steffanie; Varga, Daniel P; Lenart, Nikolett; Kallabis, Sebastian; Göb, Vanessa; Stegner, David; Escaig, Raphael; Nicolai, Leo; Franzmeier, Nicolai; Meissner, Felix; Denes, Adam; Liesz, Arthur (2026): Blocking microglial reactivity via purinergic receptors prevents subacute cognitive deficits after TIA. EMBO Molecular Medicine, 18 (4). pp. 1150-1173. ISSN 1757-4684

Abstract

Our research presents a new animal model of transient ischemic attack (TIA) that mimics brief episodes without cell loss, but results in neuronal and behavioral deficits. We identified excessive microglial reactivity, driven by acute ATP release, as a key factor in post-TIA neurological deficits, which were ameliorated by inhibiting the P2Y12 receptor, a microglia-specific purinergic receptor in the brain parenchyma responsible for activity-dependent microglial cell-cell interactions. This finding suggests that modulation of microglial reactivity offers a promising strategy to prevent cognitive impairment in TIA patients, opening avenues for future research in this underexplored area.

• Doc-Type: Article (LMU Hospital)
• Organisational unit (Faculties): 07 Medicine > Munich Cluster for Systems Neurology (SyNergy); 07 Medicine > Medical Center of the University of Munich > Institute for Stroke and Dementia Research (ISD)
• DFG subject classification of scientific disciplines: Life sciences
• DFG: Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 390857198
• DFG: Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 491502892